Despite the need for improvement in the therapy of pancreatic cancer (non-endocrine), there is very little published information on the handling of chemotherapeutic drugs by the pancreas or by adenocarcinoma of the pancreas. Furthermore, the response to chemotherapy of pancreatic adenocarcinoma has been difficult to evaluate by means of clinical trials, in part because of the frequency of far-advanced or non-measurable disease in this disorder. Thus, experimental approaches aimed at corrrecting these deficiencies would appear to be warranted. The study proposed herein would focus on the relationship between the tissse uptake and disposition (including metabolism) of chemotherapeutic agents by the pancreas and pancreatic carcinoma and the antitumor activity of these agents. Two animal tumor models have been chosen as appropriate (because of their correspondence to two types of human pancreatic adenocarcinoma) for the the investigations: a) a ductal adenocarcinoma, passaged in inbred Syrian hamsters (courtesy of Drs. Rao and Scarpelli, Northwestern University, and b) an acinar adenocarcinoma, passaged in Fischer 344 rats (courtesy of Drs. Reddy and Rao, Northwestern University). Initial investigations will be carried out with drugs that have shown some activity in pancreatic cancer--i.e., Adriamycin, 5-fluorouracil, and mitomycin C. (Preliminary experiments in my laboratory in normal Fischer 344 rats show a relatively high uptake of Adriamycin and long tissue half-life in the pancreas.) Later would involve drugs that have not received adequate clinical trial in pancreatic cancer, but that have a fairly broad spectrum of activity --namely, methotrexate, actinomycin D, vincristine and vinblastine. Such studies could be extended to include other drugs, especially those of an investigative nature. The ultimate goal of the project is to provide information that would permit more rational and informed clinical trials and to provide a basis for the understanding of the sensitivity and/or resistance of pancreatic cancer to chemotherapy.